Mutant mouse strains as models for in vivo radiotracer evaluations: [11C]methoxytetrabenazine ([11C]MTBZ) in tottering mice.
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The regional brain distribution of [11C]methoxytetrabenazine ([11C]MTBZ), a high affinity radioligand for the vesicular monoamine transporter, has been examined in normal and tottering mice, which are neurological mutants. The tottering mice show significantly higher radiotracer accumulation (150-195% of controls) in all brain regions examined (striatum, cortex, hippocampus, hypothalamus, cerebellum and thalamus). The increases in [11C]MTBZ binding correlate (r = 0.91) with the reported increases in norepinephrine concentrations in these regions, and are consistent with the noradrenergic hyperinnervation characteristic of the tottering mutant mouse. These studies demonstrate that a mutant mouse model of increased innervation can be used to evaluate the sensitivity of an in vivo radiotracer measure, in this case [11C]MTBZ binding to vesicular transporters, to an increase in the numbers of binding sites in specific regions of the brain.